The University of Toronto has found a pathway to better control the preclinical generation of main neurons depleted in Parkinson’s disease, pointing towards a new way to approach a condition with no cure and some effective treatments.
The scientists used an antibody to particularly activate a receptor in a molecular signaling way to develop dopaminergic neurons. These neurons commonly produce dopamine, a neurotransmitter important to brain health.
Researchers around the globe have been working to coax stem cells to transform into dopaminergic neurons to replace those lost in patients with Parkinson’s disease. However, the efforts are being hindered in part by an inability to target specific receptors and areas of the brain.
The director of the Donnelly Centre for Cellular and Molecular Biology and principal investigator on the study said, “We used synthetic antibodies that we had previously developed to target the Wnt signaling pathway.”
And also Professor Leslie Dan Faculty of Pharmacy and the Temerty Faculty of Medicine said, “We can selectively activate this pathway to direct stem cells in the midbrain to develop into neurons by targeting specific receptors in the pathway” and holds the Charles H. Best Chair of Medical Research at U of T. “This activation method has not been explored before.”
This study was recently published in the journal Development.
After Alzheimer’s, Parkinson’s disease is the second most common neurological disorder, affecting over 100,000 Canadians and beyond. It solely impacts older men, progressively impairing movement and causing pain, as well as sleep and mental health concerns.
Most recent research efforts to activate the Wnt signaling pathway have relied on a GSK3 enzyme inhibitor. This method includes multiple signaling pathways for stem cell proliferation and differentiation, which can lead to unintended effects on the newly produced neurons and the activation of off-target cells.
Andy Yang the first author of the study and a PhD student at the Donnelly Centre, said, “We developed an efficient method for stimulating stem cell differentiation to produce neural cells in the midbrain.”
“Moreover, cells activated via the FZD5 receptor closely resemble dopaminergic neurons of natural origin.”
A further promising finding of the study was that implanting the artificially produced neurons in a rodent model with Parkinson’s disease which led to enhancement of the rodent’s locomotive impairment.
“Our next step would be to continue using rodent or other suitable models to compare the outcomes of activating the FZD5 receptor and inhibiting GSK3,” said Yang. “These experiments will confirm which method is more effective in improving symptoms of Parkinson’s disease ahead of clinical trials.”
